EFFECTS OF D-AMPHETAMINE AND PHENCYCLIDINE ON BEHAVIOR AND EXTRACELLULAR CONCENTRATIONS OF NEUROTENSIN AND DOPAMINE IN THE VENTRAL STRIATUMAND THE MEDIAL PREFRONTAL CORTEX OF THE RAT

The effects of systemically administered phencyclidine (PCP; 2.5 mg/kg , s.c.) and D-amphetamine (1.5 mg/kg, s.c.) on the extracellular conce ntrations of neurotensin-like immunoreactivity (NT-LI) and dopamine (D A) in the ventral striatum (vSTR) and the medial prefrontal cortex (mP FC) were studied in freely moving rats using microdialysis. In separat e animals, the effects of PCP and D-amphetamine on open field activity were also analyzed. PCP, but not D-amphetamine, caused a significant increase (156% over baseline) of NT-LI levels in the vSTR which was re latively short lasting, i.e., of less than 2 h duration. In contrast, both drugs significantly increased NT-LI concentrations in the mPFC by almost 100% during the same period. PCP and D-amphetamine also signif icantly increased extracellular levels of DA in the vSTR by 83 and 364 %, respectively. However, the peak effect of PCP on DA appeared later than that of D-amphetamine, i.e., at 150 and 60 min, respectively, aft er drug administration. Also in the mPFC, both PCP and D-amphetamine s ignificantly increased DA concentrations by 98 and 284%, respectively. Generally, effects on DA levels of both PCP and D-amphetamine were, i n contrast to their effects on NT-LI levels, clearly more long-lasting , i.e., of 3-4 h duration. Behaviorally, D-amphetamine produced a more pronounced, general activation than PCP, with a faster onset of activ ation, i.e. within 30 vs 90 min after administration. However, both dr ugs produced long-lasting effects on the spatial organization of behav ioral activity, which lasted for 3-4 h. In conclusion, the more pronou nced behavioral stimulation by D-amphetamine (1.5 mg/kg, s.c.) vs PCP (2.5 mg/kg, s.c.) in the rat may largely be explained by its more pote nt DA-releasing effect in the brain. Initial behavioral suppression by PCP, e.g., of rearing, as well as its rather poor locomotor stimulant action in general, might relate to release of NT in the vSTR. The lon g-lasting, behavioral disorganization by both PCP and D-amphetamine ma y, however, be related to increased release of DA rather than NT in th e mesolimbocortical areas.